Alleyn's Medical Society: Prof Matthew Hotopf on why there's no health without mental health

Mental health has a distorted appearance to the outside world, for some it doesn't even identify as a discipline. Too abstract in its treatments to fit in alongside the NHS powerhouses yet too institutional to make up a part of 'alternative healthcare' mental health, like its patients, can feel a bit isolated from the rest of us. Yet it's key to remember that WHO (the World Health Organisation) defines Health as a complete state of physical, social and mental well-being not merely the absence of disease or infirmity, our mental happiness is just as important as our physical well-being.

Professor Matthew Hotopf works at the local Maudsley Institute apcae with King's College Hospital on Denmark Hill. He has undertaken research into epidemiology (the science that studies the patterns, causes and effects of health in populations), pallative care and mortality all within mental health. Speaking to Alleyn's Medical Society this Tuesday he wanted to spread the awareness of mental health as a serious issue and the problems which have arisen from oppressive and unethical treatments such as electro-convulsive therapy and lobotomy in the past and its segregation from the rest of the healthcare system.

Historically there has been a geographic split between mental health and health. During the 18th and early 19th century the large teaching Hospitals of London were all very centrally located, with a ring of mental institutes formed around this area and the treatments available were either extremely experimental in nature or non-existent. During this time the care of mental health was extremely institutionalised, in the majority of cases the institutes which housed these patients sought not to cure them but to divide them from normal society. However our knowledge of psychiatry has developed hugely in the last 50 years and words such as 'retard' and 'imbecile' are no longer used to describe those with mental disorders or learning disabilities. The publishing of the white paper 'Valuing People' in 2001 saw one of the greatest steps forward in the government supporting people with mental health and is a mark of the progress made within the NHS.

Prof Hotopf talked about how mental health was involved with other aspects of healthcare and his job; a large number of A&E patients suffer from PTSD and depression. This means Prof Hotopf is often involved with working alongside colleges in other departments, he noted how this kind of work has made headlines recently as the women who took her own life and that of her newborn child's was suffering from a major perinatal disorder, something he has often come across.

To finish Prof Hotopf considerig how mental health can affect life expectancy and showed us how people with mental diseases are 3-5 times more likely to suffer depressive related conditions and have life expectancies up to 20 years shorter. He stressed that these statistics highlighted the importance of our mental health and of how it affects our health as a whole, in other words there is no health without mental health.


For further reference about mental health see 'The Man Who Mistook His Wife for a Hat' By Oliver Sacks

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/250877/5086.pdf
-'Valuing People' the White Paper published 2001

See the 2010 BBC 4 documentary 'Mental: A History of the Madhouse' for information about the Victorian psychiatry treatments.

-Izzie

Alleyn's Medical Society: Mr Ahmed on 'Through the Google Glass'

A seemingly tradition and disciplined medical profession surgery is perhaps one of the most fast paced and constant in terms of change of all medical disciplines. Alternative and innovative methods constantly come into practise each year and can help to improve the rates of success immensely. New techniques such as key hole surgery and gastric bypasses have seen revolutionary changes in the profession and it is this evolution of proficiency and ability which makes the career so exciting.

Mr Ahmed works as a consultant colorectal surgeon, working mainly to remove cancerous lumps from the rectal areas. He is also the first ever surgeon to broadcast surgery live to 14,000 students using a 'google glass'. The basis for this avant-garde idea comes from a lack of first hand experience of surgery amongst medical students. The extortionate costs of medical school seem wildly disproportionate when you learn how difficult it is for students to catch a glimpse of the action going on in surgeries at the cutting forefront of medicine. Based on this problem Mr Ahmed has given students the perfect view, directly transmitting his own line of site during surgery worldwide. This allows students to access a view they would normally never have the opportunity to and allows them to become more experienced and educated. The project labelled as 'Virtual Surgeons' has been hugely successful worldwide, with the most viewers coming in from more isolated countries where students lack access to surgery. The first surgical procedure received attraction from 300 newspapers in 30 different languages and even gained a segment on ITV news at ten, in addition #googleglass trended on twitter and 'Virtual Surgeons' became the 4th reason why London is the tech capital of the world according to the magazine 'Entertainment Weekly'.

The idea has been taken even further than just simply transmitting information though as students can text questions to the surgeon during procedures and receive feedback. The project is also now being integrated into some curricula including Queen Mary's University's medical programme.

The project has potential yet and could lead on to further developments to do with broadcasting medical practise. There are however some issues being provoked by this idea as some professionals are questioning the privacy issues and pressure for a surgeon that could be invoked by broadcasting surgery. It is also key to remember that lives are saved by doctors and not just technology; overreliance on this miraculous idea could have potentially devastating consequences. Yet this beautifully simple idea, elegantly executed has proven the amazing potential technology has within surgery and healthcare.

-Izzie

Alleyn's Medical Society: Mrs Heimann on Childcare and Development

Compassion and skill go hand in hand when it comes running a children's ward and the skills required to treat children vary hugely from their adult counterparts. The age of patients makes childcare a particularly sensitive and often emotional job for those who work there and nurses on a children's ward will come face-to-face with a variety of new challenges each day.

Mrs Heimann trained as a nurse at the Royal College of Nursing, Manchester University. She specialised in Child Health Nursing, has been involved in the production of  a number of papers on childcare and has worked on children's wards at a number of locations including our local Guy's and Thomas' Hospital. She now works as a course director at the London South Bank University.

Mrs Heimann began by discussing the key differences between treating children and adults. By nature children are far more vulnerable. Not only do they have a greater surface area and so are at a greater risk of dehydration and hypothermia due to loss of heat and fluids but their organ systems are immature and exposed to the foreign pathogens we as adults have built up some resistance to. Mentally children are also underdeveloped and so it can pose a serious challenge for nurses to communicate with children and gain an understanding of their basic needs. Parents and carers are often essential sources of information for a healthcare worker to build up a picture of how a child is acting differently and gain a diagnosis, instruments like pictured pain scales can also be used to estimate the amount of pain a child is experiencing.

Mrs Heimann then went on to speak about the difference between stages of development in children using the Piaget Cognitive Theory as a crude outline for her explanations. Piaget was the first psychologist to make a systematic study of cognitive child development using simple but ingenious tests to reveal different cognitive abilities. This theory helped to eradicate the common assumption that children are just less competent thinkers than adults and is now used in both healthcare and education to utilise resources more efficiently for a child's needs, Mrs Heimann did however note that this system is far from perfect and whilst approaching a situation, common sense and intuition are just as important in handling complications to do with children.

After describing her experience working on a children's mental health ward Mrs Heimann noted how many children only require simply yet providable measures such as a set routine, care. attention and cleanliness to recover from conditions such as persistent bed wetting and depression. Mrs Heinmann poignantly went on to describe how young babies suffering from depression can often after a period of crying fall silent, not mistakenly out of exhaustion or relief, but as they have completely lost hope a parent will return to them. It is these everyday emotional experiences that can often make childcare a very difficult speciality and one where a boundary should remain between patient and nurse. Not only to respect a parents role but to allow childcare workers some relief from emotional attachment and its often distressing consequences.

-Izzie

Alleyn's Medical Society: Professor Bewley on Reproductive Ageing

Obstetrics deriving from the Latin 'to stand by' is a medical specialty that deals with pregnancy, childbirth and newborn care. Today, more than ever, the face of the specialty is changing with the introduction of radical new treatments such as IVF (in-vitro fertilization) surging in popularity and an increase in birth complications due to 'reproductive aging'.

Susan Bewley is a professor of complex obstetrics at King's College Hospital, throughout her career she has dealt with the full spectrum of 'tricky' births from emergency c-sections (a baby is delivered through an incision in a mother's abdomen) to eptopic pregnancy (where an embryo implants somewhere other than the womb). Today she came to talk to Alleyn's School Medical Society about the changing age of reproductivity among women, the consequences of delaying child-birth for later life and whether women should feel intimidated by such statistics and obliged to have children at younger ages for the sake of their own safety.

Addressing an impressive turnout of 30+ pupils and teachers Professor Bewley began by discussing the statistics behind pregnancy. A staggering 25% of pregnancies end in miscarriages, a fact she felt was concealed within everyday society by the very private and tragic nature of the ordeal; while some miscarriages are barely noticeable many are a traumatic experience for both a mother and her partner. Data demonstrates a correlation between birth complications and age as well as a decline in fertility throughout life, so why do women choose to give birth later? Perhaps it is our dependency on the miraculous nature of modern healthcare or the timeless nature of technologies, giving us the ability to 'freeze' our eggs for later life. But these technologies are misleading, whilst  eggs will remain healthy frozen outside a woman's body, the aging process that naturally occurs still creates a high risk factor for aging women who use cryogenically frozen eggs from earlier life to become pregnant in their 40s.

In addition Professor Bewley demonstrated her awe at the change she has seen within the profession within 30 years of working as an obstetric doctor. Today women unable to give birth can undergo IVF treatment where previously they would have just been turned away from clinics. There has been a gradual decline in infant mortality rates within the UK, yet Professor Bewley noted these figures are hardly reflected in countries with underdeveloped healthcare systems and a lack of support and facilities that we so often take for granted.

Even after presenting a series of slides addressing the issues of pregnancy in later life Professor Bewely noted that it is a women's decision and not the NHS's data that should be helping a woman decide when to have children. With more women in full-time careers than ever before we should appreciate that these decisions can be difficult to come to. Women's closing window of fertilization is just another unfair reality we face in today's society. 

-Izzie




IVF 

How We Live and Why We Die: the secret lives of cells- Book Review

Lewis Wolpert is a South-African born British author known for his biological literary publications which include The 'Triumph of the Embryo' and 'Why Can't a Woman Be More Like a Man?' as well as 'How We Live and Why We Die'.

Wolpert's densely scientific and comprehensive overview of the workings of the cell will give anyone a developed and in depth knowledge strongly grounded within scientific ideals. Whilst the book is complex at times it delivers a great sense of achievement and understanding for the reader that perhaps would take longer to be gained from biological textbooks. Wolpert brings the workings of the cell to life, distinguishing this science from any logical kind of order and presenting a world without finite possibilities within the smallest living unit, the cell.

An extremely popular book amongst other a-level biologists 'How We Live and Why We Die' will probably answer all the long-abided curiosities and questions any budding biologist harbours. How do cells die, reproduce and grow, or indeed on an even greater level how did cells come to exist, and why do they exist? Wolpert provides a strong scientific grounding on the cell's mechanisms which will allow you to spring board your way easily into more comprehensive and complex reading and ideas.


- Izzie

Life at the Extremes: the Science of Survival

As an A-level student I have found it hard to find a scientific book which perfectly sets the tone between excitement and education, being both engaging and readable and broadening my knowledge. Frances Ashcroft’s ‘Surviving at the Extremes’ sets this tone superbly as her own passion really comes across in each chapter which takes the reader to another of Earth’s extremes. Ashcroft documents her own experience alongside interesting and absurd case studies that help to bring the complex physiology of the human body to life in a book that has the reader in awe at the tenacious nature of life on Earth. Not only does this book help explain simple yet strange problems such as how do you go to the loo in space and how deep can we really swim but it explores a more philosophical approach as well questioning the possibility of future exploration and evolution. Your own curiosity will be quenched by Ashcroft’s various descriptions of death by cold, pressure, heat etc. and how your body will break down in this process. Whilst this is a grave topic the book is still fairly light hearted in nature and a great read for anyone irrespective of scientific understanding and ability.  

-Izzie

What Are The Effects of Organophosphorous Nerve Agents On The Human Body And What Is Their Potential As Weapons of Mass Destruction?

I wrote this research essay to be submitted to my school's competitive research prize, whilst I doubt it's winning material I have thoroughly enjoyed researching such an interesting aspect of chemical warfare and hope you find some interest in reading it. Be warned it is fairly dense.

Abstract

In today’s society it is generally assumed that nerve agents constitute yet another part of the growing international arsenal of radical new weapons that have begun to emerge in the last one hundred years. In reality, few people truly appreciate the menacing nature of these agents and their potentially devastating impact upon warfare and our everyday lives. This review aims to examine the mechanism of the action of organophosphorous nerve agents on the human body and why this makes them an effective weapon of mass destruction.

It is the fear of this strange and under researched area of chemical weaponry within society that has incited me to examine the science behind these agents in order to expose their true potency. In particular I concentrated on the nerve agent sarin throughout my research which has attracted media attention recently due to its impact on the Syrian conflict during August 2013.

From synthesis to symptoms and system disruption I have drawn research from medical textbooks, articles and journals alike to gauge a full depiction of the effects of this poison on the human body as well as recent and past case studies of its use in combat to identify why it is an effective killer.  It is from these conclusions that one can begin to envisage the true effects of nerve agents and how their use has previously and may consequently lead to devastation.

Gas! Quick Boys! – An ecstasy of fumbling,/Fitting the clumsy helmets just in time;/But someone still was yelling out and stumbling,/ And flound’ring like a man in fire or lime[1]

Owen’s work poignantly illustrates that chemical weapons are both serene and relentless in their pursuit and horrifically violent in their attack on the human body. Seemingly unattached from the noisy and violent artillery that goes alongside them, modern day soldiers know not to underestimate the danger chemical warfare poses.

It was nefarious wartime rivalry between the axis and ally powers that led to the initial production of organophosphorous nerve agents, first developed in secrecy during the inter-war years and World War II. Synthesis of the first organophosphorous nerve agent, tabun (commonly by its old NATO name GA), occurred in 1936 due to the efforts of the German researcher Gerhard Schrader at an I.G. Farbenindustrie chemical production plant, in Wuppertal-Elberfeld.[2] Whilst experimenting with organophosphorous insecticides, he noted the toxicity from the Tabun vapours on himself and amongst colleagues who all experienced mild discomfort and miosis[3]- the exceptionally toxic nature of the compound highlighted its potential use as an agent of warfare. Two years on and in 1938 the most prominent of all organophosphorous nerve agents, sarin (commonly known by its old NATO name GA), was synthesised and named with an etymology of those influential and active in its creation- Schrader, Ambros, Rudriger and van der Linde. Shortly after this the nerve agents VX and soman were also produced. Fortunately for allied forces the Germans didn’t have the opportunity to utilise these resources properly before the end of the war in 1945. [4]

Banned worldwide under the Chemical Weapon’s Convention of 1994 nerve agents are extremely toxic both dermally[5] and when inhaled or swallowed.[6] The majority of nerve agents are classed within the group organophosphorous compounds (degradable chemical compounds containing a phosphorous-carbon bond) which also includes compounds commonly found throughout medicine and pharmacology as well as agriculture. Examples of such include the anti-cancer drug cyclophosphamide[7], flame retardents such as triphenyl phosphate[8] and the pesticide diethyl-parathion[9]. In fact all organophosphorous nerve agents have developed from and are closely related to many of the commonly used organophosphorous insecticides examples of which include parathion and malathion[10]. Both insecticides and nerve agents work based on the same cellular mechanisms and inhibit the same family of enzymes, cholinesterases. Nerve agents can however be clearly defined as distinct from insecticides as they are far more toxic in nature. An in vitro study reveals that the nerve agent sarin has 1,000 fold more inhibitory activity on cells than the common insecticide parathion, both however were coincidentally produced by the same company in Germany, IG Farbenindustrie, in the 1930’s.[11]

Today in 2014, despite multiple efforts of international powers, the armamentarium of many countries is still known or suspected to include nerve agents though they are banned as a weapon of mass destruction. It is indeed realistic for soldiers going into combat to prepare for such an attack and suspect they might come face to face with chemical warfare. Whilst nerve agents are liquid at room temperature hence the common misconception ‘nerve gas’, they can be produced as an aerosol and so contact to vapour is the most common exposure route experienced among casualties.[12] To comprehend the danger of nerve agents action on the body it is first key to understand that a nerve agent is an organophosphorous compound that prevents normal nerve transmission. On introduction to the agent the triad of the eyes, nose and lungs begin to show progressively more intensive and dangerous symptoms with rhinorrhea[13], miosis and ‘tightness in the chest’ as muscular control is lost. As exposure is prolonged a casualty may notice dim vision, profuse secretion from the nose and mouth as well as dyspnea[14]. With severe exposure a casualty is most likely to fall unconscious immediately and experience intense bronchial spasms; this can lead to death by asphyxiation.[15] On a basic cellular level, nerve agents act by inhibiting the action of enzymes in the cholinergic nervous system, this being all nerve tissue where the molecule acetylcholine acts as a neurotransmitter. In vertebrae the cholinergic nervous system comprises all neuromuscular junctions, where signals cross a synapse from the central nervous system to muscle fibres. [16]

Nerve agents are grouped under the class cholinesterase inhibitors, which also includes insecticides and herbicides. Working like many other well known poisons, nerve agents inhibit the action of an enzyme by binding to it and irreversibly changing its shape. This prevents the enzyme from being able to perform its function of catalysing a metabolic reaction and the molecule which is meant to be broken down by the enzyme builds up in excess. It is the excess endogenous acetylcholine neurotransmitter which leads to the toxic effects of the nerve agent on the body. Under normal conditions the enzyme acetylcholinesterase works by hydrolysing the neurotransmitter acetylcholine thus terminating its activity at the receptor site so that it may only very briefly transit a signal across the synapse. Without the action of this enzyme the levels of acetylcholine build up at the postsynaptic cleft, continuing to send impulses to the receptor, triggering a continual response and causing muscle spasm. This leads to loss of control over breathing and potential death by asphyxiation.[17] One clear example of the effects of a nerve agent can be seen in the 1995 victims of the Tokyo subway terrorist bombings. Victims reported that they thought an eclipse had occurred on leaving the station, this was owing to the uncontrollably contraction of the pupils due to exposure to sarin gas and consequently an inability to allow light to enter the eye. This clearly demonstrates the loss of muscular control exposure to nerve agents so famously produces.[18]

 The organpophosphorous nerve agent sarin inhibits the enzyme acetylcholinesterase by phosphorylating (adding a phosphate group) to the active site causing it to denature. In fig.1 we see how sarin reacts by breaking the bond of the alkyl group attached to the acetylcholinesterase molecule and forming a covalent bond to the active site. Sarin is an irreversible inhibitor so cannot diffuse in and out of the active site but will permanently inhibit the activity of this enzyme.

Nerve agents attack on a microscopic scale. They are inescapable and practically impossible to impede; no amount of rigorous training can protect a soldier from the assault on his cholinergic nervous system that comes from these acetylcholinesterase inhibitors.[20] The recent chemical attacks on the Ghouta agricultural belt outside the Syrian capital of Damascus resulted in an estimated number of 1,000 deaths last year on the night of the 21^st of August. This marks the first major chemical attack in 25 years since the Halabaj poison gas attacks in 1988. The attack saw the deadly nerve agent sarin launched into suburban areas in rockets[21] and begins to resurrect fears and questions among communities and governments concerning chemical warfare. This is a prime example of a nerve agent’s use as a weapon of mass destruction. Not only did the sarin attack result in the death of 1,000 civilians but it displaced thousands of people from their homes and produced copious numbers of casualties, treatment for which required atropine injection.[22] This is a relatively expensive drug and creates additional strain for the limited medical services already in demand across the region. In addition those who witnessed the actions of the agent may show signs of PTSD and depression throughout their life as well as the obvious grief that comes from the loss of a loved one. Across the state any sense of security among the population has been eliminated by this atrocious act of warfare.

To recognize sarin’s capability as a weapon of mass destruction it is vital to question why offensive forces in Syria chose to propel sarin rockets into the Ghouta region in preference to other chemical agents suspected to be within their arsenal. The usage of sarin over other chemical weapons such as the blister agent mustard gas is attributed to its odourless and colourless state as well as its immediate effect on casualties. Sarin begins to act on the body within seconds of inhalation, however ill-effects attributed to mustard gas exposure may not be seen for up to 6 hours after contact. This provides a greater opportunity for medical personnel to intervene and take remedial action before serious injury occurs. Consequently sarin’s immediate assault upon its victim makes it a more perilous weapon with a higher capacity for devastation. In addition, other nerve agents such as soman and tabun are less toxic in nature and have faintly fruity odours making them more detectable than the agents sarin and VX meaning they would be unsuitable for an attack of a covert nature.[23]

Sarin has seen active use in conflict around the world in the Tokyo subway terrorist attacks and more recently in Syria. Of all the organophosphorous nerve agents sarin is the second most lethal after VX but is still more widely used. An in vitro study reveals that the aerosol exposure required to cause death in 50% of the population for VX is 10mg/min/m³ whilst this value is 100mg/min/m³ for sarin vapour and four times as much for Tabun[24]. VX’s increased toxicity is due to its low volatility of 10.5mg/m³ at 25°C compared to sarin’s higher volatility of 22,00mg/m³at 25°C, which is just below that of water.[25] This increases the potentially lethal nature of VX as it will remain on a tissue’s surface for longer so is likely to cause more disruption to our nervous system, this also means it is harder to decontaminate an area from VX.

Whilst VX is a more effective weapon of mass destruction the nerve agent sarin is more frequently used within conflict because of its less enduring character. As sarin is more volatile than VX it will evaporate more readily, this reduces the danger of an area still being contaminated by the agent in the weeks ensuing an attack and also reduces the risk of aerosols of sarin being propelled by winds away from a target area and potentially against friendly forces. However with developments in technology and more intensive and outrageous conflicts developing worldwide we could see VX usage more commonly in the theatre of war.

Chemical warfare is made up of seven different groups of agents which all act in different devastating ways to cause turmoil in the body. Common agents such as the lachrymatory agents tear gas and pepper spray, used for riot control, are the only chemical agents legally accessible to civilians in some countries and are frequently used across the world. Whilst these weapons are accessible to militia and terrorists their potency is unlikely to cause any grievous or permanent harm to one’s health and their toxicity is incomparable to that of a nerve agents, thus in terms of chemical warfare they are far less effectual. Other chemical agents which have gained fame through their use in warfare include mustard gas, which is a blister agent famous for its catastrophic use in the World War I trenches and Agent Orange, famous for its use in Vietnam.[26] Mustard gas is far more gradual in its onslaught of our health than a nerve agent and so as a weapon of mass destruction it is less valuable. Agent Orange, designed as a herbicidal agent of warfare, caused major health problems among the Vietnamese population as exposure to the herbicide caused permanent mental and physical disabilities as well as cleft palate. Whilst the effects of Agent Orange caused shock among the American public this agent only affected around 20% of Vietnamese exposed to it and so would never intentionally be used as a chemical weapon when resources of other more potent compounds are available. Organophosphorous nerve agents have yet to gain the fame of these agents but nerve agents immediate and effective nature as a weapon and their extremely toxic effect on our bodies suggests they will play an influential role in future conflicts.

It is clear that nerve agents’ irreversible inhibition of acetylcholinesterase in the cholinergic nervous system poses a major threat to any casualtie’s health and it is only through early diagnosis of the primary symptoms and a thorough understanding of these poisons that an antidote such as atropine and thorough decontamination may lead to recovery. Whilst the biological mechanisms behind this process are relatively simple and mirrored by other everyday poisons, a nerve agent’s ability to cause rapid deterioration should still never be undervalued. Comparison of physical and chemical properties between the different organophosphorous nerve agents reveals why only two have seen major usage and also advocates that we may see VX’s appearance in theatre over the more commonly used sarin as weaponry systems develop. With the recent civil wars in Libya and Syria militaries have seen rises in a fraudulent and guerrilla style of warfare that points towards the possible increased usage of banned weapons such as nerve agents in the future. As a weapon of mass destruction we know these agents are extremely destructive and their characteristics make them favourable by militia over other agents such as mustard gas or indeed mortar or missiles which induce no chemical threat.

Chemical warfare instils a horror that conventional warfare cannot mimic, by contrast to artillery and small arms, death from a chemical attack is immoral, often drawn out, painful and undignified. Barack Obama himself stated that chemical warfare was the ‘red line’ that should not be crossed. Rather than reduce numbers the actions of governments seems to have flared terrorists and armies worldwide to dare to cross the ‘red line’.  Whilst warfare is by its very nature unpredictable and temptuous we’re undoubtedly going to see nerve agents play an instrumental role in the conflicts of tomorrow.

Word count (excluding abstract, quotes, footnotes and bibliography) – 2496

Bibliography

Books (4)

-          Owen, W (1994). The Poems of Wilfred Owen. Ware, Hertfordshire: Wordsworth Editions Limited

-          Sidell, F (1997). Medical Aspects of Chemical and Biological Warfare. Borden Institute: Office of The Surgeon General

-          Gilman, A et al (1982). Organophosphorous Compounds. Bartholomew Press, Dorking: Adlard and Son Ltd

-          Haruki, M (2001). Underground: The Tokyo Gas Attack and the Japanese Psyche. USA: Vintage Books

Journals (2)

-          Grob, D, Harvey, J. (1957). Effects in Man of the Anticholinesterase Compound Sarin (Isopropyl Methyl Phosphonoflouridate). Journal of Clinical Investigation

-          Wills, J. (1954). A Statistical Study of the Adamek Report. Medical Laboratory Special Report.

Internet Articles (6)

-          Katz, K. (2013). Organophosphate Toxicity. Available at: http://emedicine.medscape.com/article/167726-overview#a0101

-          Ivarsson, U. (1992). Types of Chemical Weapons: Nerve Agents. Available: http://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/nerve-agents/

-          Soderberg, T. (2012). 12.4C: Enzymatic ester hydrolysis: acetylcholinesterase and sarin nerve gas. Available: http://chemwiki.ucdavis.edu/Organic_Chemistry/Organic_Chemistry_With_a_Biological_Emphasis/Chapter_12%3A_Acyl_substitution_reactions/Section_12.4%3A_Esters

-          Bowen, J (2014). Syria Crisis: Damascus-area sarin attack, one year on. Available: http://www.bbc.co.uk/news/world-middle-east-28891307

-          British Armed Forces. (2014). UK Industry’s Chemical, Biological, Radiological and Nuclear Defence Special Interest Group. Available: http://www.cbrn-uk.com/about-us/

-          Jacobs, S. (2013). Chemical Warfare, From Rome to Syria. A Time Line. Available: http://news.nationalgeographic.com/news/2013/08/130822-syria-chemical-biological-weapons-sarin-war-history-science/  Last accessed 28th August 2014.

Visits (1)

-          Visit to the RAF Henlow Centre of Aviation Medicine CBRN unit (chemical, biological, radiological and nuclear)

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[1] Owen, W (1994). The Poems of Wilfred Owen. Ware, Hertfordshire: Wordsworth Editions Limited. pp.60

[2] Sidell, F (1997). Medical Aspects of Chemical and Biological Warfare. Borden Institute: Office of The Surgeon General. pp.130

[3] Contraction of the pupil

[4] Sidell pp. 130-131

[5] To come into contact with the skin’s surface

[6] Sidell pp.142-147

[7] Gilman, A et al (1982). Organophosphorous Compounds. Bartholomew Press, Dorking: Adlard and Son Ltd. pp.146

[8] Gilman, A pp.269

[9] Katz, K. (2013). Organophosphate Toxicity. Available: http://emedicine.medscape.com/article/167726-overview#a0101 Last accessed 1st September 2014.

[10] Katz, K

[11] Grob, D, Harvey, J. (1957). Effects in Man of the Anticholinesterase Compound Sarin (Isopropyl Methyl Phosphonoflouridate). Journal of Clinical Investigation, pp.350-368.

[12] Sidell pp. 142

[13] More commonly known as a runny nose

[14] Shortness of breath

[15] Ivarsson, U. (1992). Types of Chemical Weapons: Nerve Agents. Available: http://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/nerve-agents/ Last accessed 28th August 2014.

[16] Sidell pp. 132

[17]Sidell pp. 142-144

[18] Haruki, M (2001). Underground: The Tokyo Gas Attack and the Japanese Psyche. USA: Vintage Books p. 30-45

[19] Soderberg, T. (2012). 12.4C: Enzymatic ester hydrolysis: acetylcholinesterase and sarin nerve gas. Available: http://chemwiki.ucdavis.edu/Organic_Chemistry/Organic_Chemistry_With_a_Biological_Emphasis/Chapter_12%3A_Acyl_substitution_reactions/Section_12.4%3A_Esters Last accessed 29th August 2014.

[20] Sidell p. 131

[21] Bowen, J (2014). Syria Crisis: Damascus-area sarin attack, one year on. Available: http://www.bbc.co.uk/news/world-middle-east-28891307 Last accessed 29th August 2014.

[22] Sidell pp. 159

[23] Sidell pp. 141-142

[24] Wills, J. (1954). A Statistical Study of the Adamek Report. Medical Laboratory Special Report. (54).

[25] Sidell p. 141

[26] Jacobs, S. (2013). Chemical Warfare, From Rome to Syria. A Time Line. Available: http://news.nationalgeographic.com/news/2013/08/130822-syria-chemical-biological-weapons-sarin-war-history-science/  Last accessed 28th August 2014.

-Izzie

 

The Discovery, Developement and Controversy of the Anti-cancer Drug Taxol

Paclitaxel or Taxol is a mitotic inhibitor used as chemotherapy treatment for patients with lung, breast, ovarian, head, neck and other types of solid tumour cancer. In addition it can be used to treat advanced Kaposi’s sarcoma (a rare type of cancer) and to prevent restenosis (recurrence of stenosis, narrowing of the blood vessels). It is one of the most widely used anticancer agents in the world and according to the World Health Organisation (WHO) it is one of 350 essential medicines needed in any basic healthcare system.

Taxol was discovered in 1966 in a US National Cancer Institute (NCI) program at the Research Triangle Institute in North Carolina when Monroe Wall, Mansukh Wani and their colleagues isolated it from the bark of the Pacific Yew tree, Taxus brevifolia, naming it Taxol.Their findings were announced at an American Chemical Society meeting in Miami Beach in April of 1967.  The results and chemical structure were published in 1971.

The NCI found themselves under pressure to collect more Taxus bark so as to isolate larger quantities of Taxol for use in studies but in 1969 1,200kg of bark yielded only 10g of pure material. Harvesting the bark from the Pacific Yew Tree killed it in the process. Through the 1970s Taxol began to rise to fame in the scientific community as studies undergone by NCI researchers as well as cell biologists showed it to be an extremely effectiveanti-cancer agent. The increasing interest surrounding Taxol led to the NCI collecting pure material from 10,000kg of the Pacific Yew Tree bark. Animal toxicology studies of the drug were completed by 1982 and clinical trials began in 1984.

By May 1988 the drug had shown an effect in melanoma patient and had had a remarkable response rate of 30% in ovarian cancer patients, considering the drug was still be developed at the time this. At this point the NCI calculated to produce enough Taxol to treat every melanoma and ovarian cancer patient in the US would require the destruction of 360,000 Pacific Yew trees, the problems associated with supplying Taxol became suddenly all the more serious. From 1967 to 1993 all Taxol was produced from the bark of the Pacific Yew Tree but by 1992 there were now 30 teams working to synthesise Taxol using different methods. This was driven not only by the need for more practical commercial production of the drug but to produce more chemical understanding surrounding it. The Holton Taxol total synthesis method was discovered in 1994 and marked the end of the destruction of Pacific Yew Trees for the retrieval of this life changing drug.

-Izzie

Dorothy Hodgkins

I have to shamelessly admit before seeing her 'Google Doodle' celebrating the scientists 104th birthday yesterday I had no idea who Dorothy Hodgkin was, my knowledge of key female scientists stretched about as far as Marie Curie and Rosalind Franklin. After a bit of reading ad scrolling through various wikipedia articles I discovered that she's the only British women to have won a noble prize in a science category and one of only four women to have won a noble prize in chemistry (the others being Marie Curie, her daughter Irene Joliot-Curie and most recently in 2009 Ada E. Yonath).

Hodgkin studied at Oxford and then went on to do PhD at Cambridge, it is there that she first became interested by the potential of X-ray crystallography to determine the structure of proteins. Her most notable achievement is the discovery of the structure of penicillin in 1945 which she published in 1949 and her analysis and work into the structure of the vitamin B12. On the day of her noble prize award in 1964 the Daily Mail reported 'Oxford Housewife wins Nobel!', a somewhat degrading headline for a pioneering scientist. She held her post as a fellow and tutor in chemistry at Oxford for an impressive 41 years, till 1977. During the 1940s one of her students was Margaret Roberts, the future Prime Minister Margaret Thatcher, who installed a portrait of Hodgkin in Downing Street in the 1980s.

Hodgkin died in 1994 from a stroke in her home at Warwickshire. Her work on X-ray crystallography became a widely used tool and was critical in later determining the structures of many biological molecules where knowledge of stucture is critical to an understanding of function. Also notably Hodgkin was also one of five 'Women of Achievement' selected for a set of British stamps issued in August 1996 and again in 2010, during its 350th anniversary, the Royal Society celebrates with the publication of 10 stamps of some of its most illustrious members, bestowing Professor Hodgkin wit her second stamp. She was in the company of nine men. 

-Izzie